Further testing of the hypothesis concerning the role of cellular glycoconjugates in promotion is focused on changes in cell surface glycolipids particularly gangliosides. The rationale for investigating these sialic acid containing glycolipids is that 1) phorbol esters are known to produce specific ganglioside changes under conditions in which they regulate expression of differentiation and 2) binding to specific surface gangliosides is required for the biological function of a number of regulators of cellular growth and differentiation including certain hormones. Recent results on this project have shown that tumor promoting but not nonpromoting phorbol esters produce specific changes in ganglioside synthesis principally a 10-fold decrease in the net synthesis of a trisialoganglioside (GT). This change is competely blocked by anti- promoting concentrations of retinoic acid. Furthermore, JB6 variants which are promotable to tumor cell phenotype by phorbol esters consistently show the decrease while their nonpromotable counterparts do not, suggesting that a ganglioside shift may play a causal role in promotion of neoplastic transformation.